What side effects are associated with this type of intervention?

Common treatments for leukemia, such as azacitidine and other hypomethylating agents, often result in side effects including cytopenias (reduced blood cell counts), febrile neutropenia (fever with low white blood cell count), and gastrointestinal disturbances. Patients frequently experience fatigue, nausea, and injection site reactions. Severe side effects can include infections due to immunosuppression, liver and kidney function abnormalities, and the need for hospitalization due to neutropenic fever. Monitoring blood counts and organ function is essential to manage these adverse effects.

What prior FDA approvals exist?

Azacitidine, a DNA methyltransferase inhibitor, has been FDA-approved for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Decitabine, another DNA methyltransferase inhibitor, is also FDA-approved for similar indications. These drugs work by inhibiting DNA methylation, which can reactivate tumor suppressor genes and induce cancer cell death. Venetoclax, often used in combination with azacitidine or decitabine, has also been approved for AML treatment, particularly in patients who are not candidates for intensive chemotherapy. These treatments are similar to the combination being studied in the ASTX030 trial, where cedazuridine is used to increase the bioavailability of azacitidine.

What other types of research exist?

Promising alternatives to ASTX030 for leukemia patients include: 1) Venetoclax combined with azacitidine, which has shown efficacy in AML patients with poor-risk cytogenetics and TP53 mutations. 2) Low-dose cytarabine (LoDAC) combined with venetoclax or glasdegib, particularly for patients who are not candidates for HMA-based treatment. 3) Decitabine plus bortezomib, although it did not improve response rates or survival in a phase 2 study, it remains a consideration. These alternatives offer different mechanisms of action and may be suitable based on individual patient profiles and specific leukemia subtypes.

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Anti-metabolites

Cedazuridine + Azacitidine for Leukemia

Phase 2 & 3

Waitlist Available

Research Sponsored by Astex Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤2.5 × ULN.

For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD) and must be ≥2 weeks off systemic immunosuppressive therapy before start of study treatment.

Must not have

Participants with MDS/MPN who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.

Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new pill form of two drugs, cedazuridine and azacitidine, for patients needing azacitidine treatment. The goal is to see if the pill is as effective as the injection. Cedazuridine helps azacitidine work better by preventing its breakdown, and azacitidine stops cancer cells from growing.

Who is the study for?

This trial is for adults with certain blood disorders like MDS, CMML, or AML who can benefit from azacitidine treatment. They should be physically stable (ECOG 0-1), expected to live at least 12 weeks, able to swallow pills and fast for 4 hours. Pregnant women can't join; participants need proper liver and kidney function and no recent major surgeries or chemotherapy.

What is being tested?

The study tests ASTX030 (oral cedazuridine combined with azacitidine) against subcutaneous azacitidine alone in three phases: dose escalation, dose expansion, then a randomized comparison of the final oral dose versus the injection form over approximately four years.

What are the potential side effects?

Potential side effects include typical reactions associated with cancer treatments such as nausea, vomiting, diarrhea, constipation, fatigue. There may also be risks related to low blood counts leading to increased infection risk or bleeding complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver function tests are within the required range.

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I had a stem cell transplant without GVHD and haven't taken immunosuppressives for 2 weeks.

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I can carry out all my daily activities without help.

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My condition is a specific type of blood disorder according to certain classifications.

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I am not pregnant or breastfeeding and my pregnancy test was negative.

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My kidneys work well enough to clear waste from my blood.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have MDS/MPN and can feel swelling in my liver or spleen.

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I have other serious health issues or infections that are not under control.

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I haven't taken any experimental drugs recently or have ongoing side effects from them.

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I have an active stomach or upper small intestine ulcer that's not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Total cycle area under the curve (AUC)0-24 exposures

Secondary study objectives

AML-free survival for participants with MDS, CMML, or MDS/MPN

Best clinical response rate for participants with AML

Best clinical response rate for participants with MDS, CMML, or MDS/myeloproliferative neoplasms (MPN)

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase 3, Sequence BExperimental Treatment2 Interventions

Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3)

Group II: Phase 3, Sequence AExperimental Treatment2 Interventions

Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3)

Group III: Phase 2, Sequence BExperimental Treatment2 Interventions

SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3)

Group IV: Phase 2, Sequence AExperimental Treatment2 Interventions

Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3)

Group V: Phase 1, Stage B (Dose Expansion)Experimental Treatment1 Intervention

Oral cedazuridine + azacitidine will be administered separately at the recommended dose for expansion (RDE)

Group VI: Phase 1, Stage A (Dose Escalation)Experimental Treatment3 Interventions

In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

Cedazuridine

2021

Completed Phase 1

~40

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Hypomethylating agents (HMAs) such as azacitidine and decitabine are commonly used in the treatment of leukemia. These drugs work by inhibiting DNA methyltransferase, an enzyme responsible for adding methyl groups to DNA. This inhibition leads to the reactivation of tumor suppressor genes and the induction of cellular differentiation and apoptosis in malignant cells. Cedazuridine, studied in combination with azacitidine in the ASTX030 trial, increases the bioavailability of azacitidine by inhibiting its degradation in the gastrointestinal tract, allowing for effective oral administration. This is significant for leukemia patients as it offers a less invasive and potentially more convenient treatment option compared to traditional intravenous or subcutaneous administration.